title: Concentration-dependent killing of antibiotic-resistant pneumococci by the methoxyquinolone moxifloxacin.
abstract: The in-vitro activity of the methoxyquinolone moxifloxacin (Bay 12-8039) was compared with that of ciprofloxacin, levofloxacin, norfloxacin, ofloxacin and sparfloxacin against 220 pneumococcal isolates. Moxifloxacin was more active than the comparator quinolones against all strains including 60 strains intermediately susceptible to penicillin, 60 strains resistant to penicillin and 40 strains resistant to the macrolides. When the activity of the moxifloxacin was compared with that of oral beta-lactams, macrolides and azalides used to treat respiratory infections, the drug was as active as penicillin, co-amoxiclav and cefuroxime against penicillin-susceptible strains and as active as clarithromycin and erythromycin against macrolide-susceptible strains. The drug was more active than any oral beta-lactam agent against intermediate or fully penicillin-resistant strains and more active than any of the macrolides against macrolide-resistant strains. In time-kill assay studies, moxifloxacin showed concentration-dependent killing at about the MIC. The mean log10 reduction in colony count for nine strains each tested in triplicate was 1.2 log10 after 6 h of incubation at 2 x MIC of moxifloxacin. The log10 killing at 6 h increased to 2.74 log10 at 4 x MIC, 3.75 log10 at 8 x MIC and 4.17 log10 at 16 x MIC. Because of the enhanced potency of this quinolone against pneumococci, concentrations of 8 x MIC90 were achieved at 0.48-0.96 mg/L. These data suggest that orally administered moxifloxacin is likely to be highly active at physiological concentrations against penicillin- and macrolide-resistant pneumococci.
authors.affiliation: MRC/SAIMR/WITS Pneumococcal Diseases Research Unit, Johannesburg, South Africa. 174klug@mail.saimr.wits.ac.za
authors.forename: K P
authors.initials: KP
authors.lastname: Klugman
authors.forename: T
authors.initials: T
authors.lastname: Capper
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D002511:Cephalosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D010403:Penicillin Resistance; D010406:Penicillins / Q000494:pharmacology; D011804:Quinolines; D015363:Quinolones / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D002511:Cephalosporins; D024841:Fluoroquinolones; D010406:Penicillins; D011804:Quinolines; D015363:Quinolones; D000077266:Moxifloxacin